Telomeres, the specialized nucleoproteic structures, cap and protect chromosomes from DNA degradation and end-fusion which can lead to chromosomal breaks and recombination. In telomerase-negative cells, each time a cell divides, the telomeres become shorter. When the telomeres get too short, the cell can no longer divide and ultimately leads to cellular senescence and death.
Studies have shown that diseases involving oxidative stress, inflammation and increased cell renewal are additional environmental factors that can accelerate telomere shortening and, at least in part, accelerate physiopathological processes. These diseases include, but are not limited to, autoimmune and immune-mediated diseases, inflammation diseases, chronic pulmonary diseases, such as, for example, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), atherosclerosis, and Duchenne muscular dystrophy (DMD).
Autoimmune and immune-mediated diseases include, for example, systemic lupus erythematosus, rheumatoid arthritis, Wegener's granulomatosis, sarcoidosis, systemic sclerosis, juvenile idiopathic arthritis, adult-onset still disease, myositis, psoriasis, atopic dermatitis, primary biliary cirrhosis, and autoimmune diabetes.
Chronic obstructive pulmonary disease (COPD), which encompasses diseases such as, for example, cystic fibrosis, chronic bronchitis, and emphysema, are steadily increasing in frequency, possibly due to continued smoking, increasing air pollution, and the continued aging of the population. For example, it has been estimated that in the United States alone, cystic fibrosis, a genetic disease, occurs in 1 out of every 2500 births, that 8 million people suffer from chronic bronchitis, and that 2 million individuals have emphysema. The number of deaths from these conditions, from both chronic disease complications and acute attacks, are continuing to increase. Moreover, deaths from just chronic obstructive pulmonary disease rose from 33,000 in 1970 to 62,000 in 1983.
IPF, which is one of about 200 diseases called interstitial lung diseases (ILDs), is a chronic, ultimately fatal disease characterized by a progressive decline in lung function. IPF usually occurs in adult individuals of between 50 and 70 years of age, particularly those with a history of cigarette smoking, affecting more men than women. IPF affects about 128,100 people in the United States, with about 48,000 newly diagnosed cases and 40,000 deaths annually.
Therefore, there remains a need for methods and compositions that overcome these deficiencies and that effectively treat short telomere disorders.